POS1314 AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION: LONG-TERM OUTCOMES IN A SINGLE-CENTER COHORT OF PATIENTS WITH SYSTEMIC SCLEROSIS
Authors: N. Del Papa, A. Rindone, S. Cavalli, A. Minniti, F. Onida, G. Saporiti, M. Goldaniga, C. Iannone, G. Armentaro, S. Germinario, M. Sette, R. Caporali
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Although various immunosuppressive drugs are used to treat Systemic Sclerosis (SSc), no therapy has proved to be actually effective in changing the natural history of the disease. Three randomized controlled trials have demonstrated the superiority of autologous hematopoietic stem cell transplantation (AHSCT) on conventional therapies for patients suffering from severe SSc. However, data on disease activity and progression after AHSCT are really scant. <h3>Objectives</h3> To retrospectively evaluate the long-term effectiveness of AHSCT in a monocentric cohort of SSc patients with a severe diffuse cutaneous disease at the baseline, and every 12 months up to 60 months after transplantation. In addition, we retrospectively compared the disease outcome of transplanted patients to an age-and sex-matched group of severe SSc patients selected from our historical cohort and treated with conventional therapies. <h3>Methods</h3> Clinical, instrumental and laboratory data of all SSc patients who underwent AHSCT between 2003 and 2020 in our center and with a regular follow up of 60 months after transplant, have been retrospectively analyzed. AHSCT was performed by mobilisation with CTX and G-CSF, selection of CD34+ cells and conditioning regimen with CTX and rabbit ATG. Survival, skin involvement assessed by modified Rodnan skin score (mRSS), cardiac and lung involvement assessed by echocardiography and lung functional parameters, and EUSTAR disease activity (EDA) scores were recorded. All transplanted patients had a rapidly progressive cutaneous disease characterized by a mRSS&gt;14 and were unresponsive to conventional immunosuppressive therapies. Similar evaluations were made in the control group represented by age- and sex-comparable patients suffering from an exactly comparable disease-duration and clinical characteristics in term of skin involvement and disease activity, and treated with conventional therapies. For this group, the enrolment period was 1991-2020. <h3>Results</h3> 35 patients underwent AHSCT, 30 females and 5 males. Patients were eligible for AHSCT when they had mRSS&gt;14 and an EDA score&gt;2, in the absence of severe organ involvement (renal clearance&lt;40mL/min, DLCO&lt;40%, ejection fraction&lt;45%). At the baseline mean, mRSS was 21.4 ± 5, mean FVC 90.1% ±17.9 and mean DLCO 66.5%±15. We observed a sustained improvement in skin thickening and a persistent reduction of EDA scores, with p-values&lt;0.0001 for both parameters at any follow up time. Transplant-related mortality occurred in 2 patients, one at +65 days from interstitial pneumonia and one at +2 days from myocarditis (5.7%). Three patients died during the follow up from disease progression complications, one at +3 years due to fatal cardiac arrhythmia and two due to progressive lung failure at + 5 years and +7 years. In the control group (68 patients), 25 patients received 6 monthly pulses of intravenous cyclophosphamide (750mg/m<sup>2</sup>), 10 received mycophenolate, 10 methotrexate, 12 rituximab, and 11 received steroids and vascular therapies, in the absence of real immunosuppressive therapies. AHSCT patients experienced a better overall survival compared with control patients (p=0.001). AHSCT was also more effective than other therapies for the outcomes of skin score (p&lt;0.0001), lung function (p=0.0004) and disease activity (p&lt;0.0001). <h3>Conclusion</h3> The results of this large historical cohort study of patients with severe SSc confirm efficacy of AHSCT in terms of survival, response to treatment and disease progression rate. The improvement of skin thickening and stabilization of organ function up to 5 years after transplantation, result in a global clinical improvement, as showed by the persistent reduction in the activity score. Probably as a consequence of an accurate patient selection, transplant related mortality results to be acceptable and similar to that reported in previous studies. Despite the limitation of a retrospective study, AHSCT is more effective than conventional therapies, including the latest immunosuppressive agents. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Nicoletta Del Papa Speakers bureau: Janssen, Boheringer-Ingelheim, ANDREA RINDONE: None declared, Silvia Cavalli: None declared, Antonina Minniti: None declared, Francesco Onida: None declared, Giorgia Saporiti: None declared, Maria Goldaniga: None declared, Claudia Iannone: None declared, Giuseppe Armentaro: None declared, Sabino Germinario: None declared, Manuel Sette: None declared, Roberto Caporali Speakers bureau: AbbVie, Amgen, BMS, Celltrion, Fresenius, Galapagos, Janssen, Lilly, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Fresenius, Galapagos, Lilly, Novartis, Pfizer, and UCB,